The present invention relates to bis-aryl carbinol derivatives, pharmaceutical compositions and methods of using such derivatives.
European Patent Application Publication Number 0235463, published Sep. 9, 1987 discloses compounds of the formula: ##STR4## wherein: Ar, D, and R can be selected from, amongst others, phenyl, substituted phenyl, pyridinyl, thienyl or furanyl; A can be, amongst others, --O--R.sup.1 wherein R.sup.1 can be, amongst others, hydrogen; Q can be absent because n can be zero; p can be one; m is 0 to 6 and can therefore be one; and B can be absent because z can be zero.
International Publication Number WO 89/10369 discloses compounds of the formula: ##STR5## wherein: one of a, b, c and d represents nitrogen or --NR.sup.11 --, wherein R.sup.11 is, amongst others, O.sup.-, and the remaining a, b, c and d groups are CH; T represents carbon or nitrogen, with the dotted line attached to T representing an optional double bond when T is carbon; when m plus n equals 1 or 2, X represents, amongst others, --O-- or --S(O).sub.e -- wherein e is 0, 1 or 2; when m plus n represents O, X can be, amongst others, any substituent for m plus n equalling 1 or a direct bond; when m plus n equals 3 then X equals a direct bond; Z represents .dbd.O or .dbd.S such that when Z is O, R may be, amongst others, ##STR6## wherein Y is N or NR.sup.11 ; when Z represents .dbd.S, R represents in addition to the R group above, aryloxy or alkoxy. U.S. Pat. No. 4,826,853 issued to Piwinski et al. on May 2, 1989 is the priority document for WO 88/03138 which published on May 5, 1988. WO 88/03138 discloses compounds of the formula ##STR7## wherein: one of a, b, c and d represents N or NR.sup.9 where R.sup.9 is, amongst others, O, and the remaining a, b, c and d groups are CH; X represents N or C, which C may contain an optional double bond to carbon atom 11; Z represents O, S or H.sub.2 such that when Z is O, R may be, amongst others, ##STR8## when Z represents S, R represents in addition to the R group above, aryloxy or alkoxy; and when Z represents H.sub.2, R can be, amongst others, ##STR9##
These compounds are disclosed as being useful in the treatment of allergy and inflammation.
In particular, WO88/03138 discloses intermediates having the formulas: ##STR10##
During the course of research on the compounds disclosed in WO 88/03138, it was generally found that the compounds having a carbonyl group (Z.dbd.O) attached to the piperidyl, piperidylidenyl or piperazinyl nitrogen atom were much stronger antagonists of platelet activating factor (PAF) than the compounds having a CH.sub.2 group (Z.dbd.H.sub.2) attached thereto.
WO 90/13548 published on Nov. 15, 1990 on PCT/US90/02251 which was filed on Apr. 30, 1990 and claims priority to U.S. application Ser. No. 345,604 filed May 1, 1989 discloses compounds similar in structure to the compounds disclosed in WO 88/03138 with the difference being that the R group represents an N-oxide heterocyclic group of the formula (i), (ii), (iii), or (iv): ##STR11## wherein R.sup.9, R.sup.10, and R.sup.11 can be, amongst other groups, H.
Galantay et al., Journal of Medicinal Chemistry, 1974, Vol. 17, No. 12, pp. 1316 to 1327 discloses oxazole and thiazole analogs of amitripyline. A disclosed intermediate has the formula: ##STR12##
U.S. Pat. No. 4,659,716 discloses an intermediate of the formula: ##STR13##
PCT/US89/01689, International Publication Number WO 89/10363. published Nov. 2, 1989, discloses compounds of the formula: ##STR14## wherein T represents .dbd.O or ##STR15## Q represents CH, N or N.fwdarw.O; ring A represents defined heterocyclic aromatic rings (see pp. 3 and 4 for example), U is --H or --OH when the bond between W and the cyclohepta ring is a single bond; W represents C, N or N.fwdarw.O and the dotted line drawn to W from the cyclohepta ring represents an optional double bond when W is C, or is absent when W is N.fwdarw.O; and X can be, amongst others: ##STR16## wherein Z is O or S; R.sup.1 can be, amongst others, H, alkyl, cycloalkyl, aryl, and heteroaryl (the definition of heteroatom includes N.fwdarw.O); and R.sup.x can be alkyl, aralkyl or aryl.